The purpose of the studies proposed in this grant is to understand the molecular mechanisms underlying polarized targeting of neuronal transmembrane proteins. The specific aims of this grant will concentrate on three main levels of polarized targeting: 1. Targeting of proteins at the plasma membrane through compartment-specific endocytosis and vesicle docking. 2. Trafficking of vesicles containing either axonal or dendritic proteins to the appropriate polarized compartment. 3. Sorting of axonal and dendritic proteins into separate vesicles. The ultimate goal of this research is to understand how these targeting mechanisms produce surface distributions of proteins that are highly polarized. Relevance Protein targeting plays an important role in many physiological processes such as the establishment and maintenance of synaptic connections. In addition, defects in trafficking are associated with numerous neurological diseases of major clinical significance such as Alzheimer's and Huntington's disease. PUBLIC HEALTH RELEVANCE: In neurons many transmembrane proteins are targeted specifically to either the axonal or dendritic compartment. The goal of this grant is to understand the molecular mechanisms that mediate this targeting.